Study: Understanding the risks of a second cancer after a breast cancer diagnosis in people with BRCA1 and BRCA2 mutations

RELEVANCE

Most relevant for: Men and women diagnosed with breast cancer who have a BRCA1 or BRCA2 mutation.

It may also be relevant for:

• people with breast cancer
• people with a genetic mutation linked to cancer risk
• previvors
• people newly diagnosed with cancer
• people with a family history of cancer

Relevance: High

Strength of Science: High

More rating details

What is this study about?

People with an inherited mutation that increases cancer risk may have more than one cancer diagnosis in their lifetimes. The risk of a second primary cancer after a diagnosis—a completely new cancer that is not a recurrence of the first cancer—is not well understood. In this study, researchers followed 26,291 people who were diagnosed with breast cancer and had genetic testing for BRCA1 and BRCA2 mutations. The goal was to understand how often people with these mutations were diagnosed with a second primary cancer. Over time, the researchers tracked whether participants were diagnosed with additional cancers, including a new breast cancer in the opposite breast, ovarian cancer, pancreatic cancer and other cancers. The findings showed that people with BRCA1 or BRCA2 mutations had a significantly higher risk of developing these second cancers compared to people without mutations, providing important insight into long-term cancer risks after a breast cancer diagnosis.

Why is this study important?

People with BRCA1 or BRCA2 gene mutations have a higher risk for multiple cancers. This study provides new information about the chance of having an additional primary cancer after breast cancer treatment. This information may help people tailor approaches to surveillance, prevention strategies and genetic counseling to better understand and manage their future cancer risks.

Study findings

Researchers looked at the medical records of people in England who had genetic testing and were diagnosed with non-metastatic breast cancer between January 1995 and December 2019. The researchers followed participants for just under four years on average to identify how many had a second primary cancer. This cancer history was then used to estimate the average chance of cancer 10 years after an original breast cancer diagnosis. People with non-skin melanoma and a second breast cancer diagnosed within 93 days of the first breast cancer diagnosis were excluded from the results.

Participants included 26,291 people (25,811 females and 480 males).

• Nearly 14% had a mutation in BRCA1 or BRCA2 (1,847 people had a BRCA1 mutation; 1,824 people had a BRCA2 mutation). Because only people who had genetic testing due to a strong family history of cancer were included, this study may have overestimated the rate of cancer in people without a BRCA1 or BRCA2 mutation.
• Participants with BRCA1 mutation:
  • 1,840 females (7%) with breast cancer had a BRCA1 mutation. The average age of a first breast cancer diagnosis among females was 39.
    • Female participants with an inherited BRCA1 mutation had higher chances of developing endometrial, ovarian and colorectal cancers, and a new breast cancer in their opposite breast than female participants without a BRCA mutation.
    • The estimated 10-year risks for additional cancers were:
      • 16%: breast cancer in the opposite breast
      • 6%: ovarian cancer
      • nearly 8%: the combined risk for all other non-breast or ovarian cancers
  •  7 males (1.4% of males with breast cancer) had a BRCA1 mutation.
    • None of these males had a second primary cancer, possibly reflecting that few men with breast cancer and a BRCA1 mutation were included in the study.
• Participants with BRCA2 mutation:
  •  1,750 females (6.7%) had a BRCA2 mutation. The average age of a first breast cancer diagnosis among females was 45.
    • Female participants with an inherited BRCA2 mutation had a higher chance of ovarian and pancreatic cancers, and a second breast cancer in their opposite breast than people without a BRCA mutation.
    • The estimated 10-year risks for additional cancers were:
      • 12%: breast cancer in the other breast
      • 3%: ovarian cancer
      • just over 6%: the combined risk for all other non-breast or ovarian cancers
  •  74 males (15% of males with breast cancer) had a BRCA2 mutation.
    • Male breast cancer survivors had increased risks of pancreatic and prostate cancers and a second primary cancer in their opposite breast.
      • 15 males (20%) had a second primary cancer: 2 had breast cancer, 7 had prostate cancer, 3 had pancreatic cancer and 3 others had cancers of an unspecified location.
• Participants with no BRCA1 or BRCA2 mutation:
  • 21,543 females and 394 males had genetic testing due to a strong family history but did not have an inherited BRCA1 or BRCA2 mutation. Testing results for mutations in other genes that increase breast cancer risk were not reported. This may overestimate cancer rates among people without BRCA1 and BRCA2. The average age of a first breast cancer diagnosis among females was 46.
  • The estimated 10-year risk of additional cancer was:
    • 3.6%: breast cancer in the opposite breast
    • 0.4%: ovarian cancer
    • just under 5%: the combined risk for all non-breast or ovarian cancers
  • 23 of 294 males (8%) had a second primary breast cancer.

What does this mean for me?

If you have a BRCA1 or BRCA2 gene mutation, this study shows that your risk of developing certain second primary cancers is higher than the risk of people without these mutations. In this study, a second primary breast cancer in the same or opposite breast was the highest risk among participants who had either a BRCA1 or BRCA2 gene mutation.

This study also showed that having a BRCA1 mutation may increase your risk of a second primary cancer: ovarian, colorectal or endometrial. If you have a BRCA2 mutation, you may also have increased risks of ovarian, pancreatic and other non-breast/non-ovarian cancers. Due to these elevated risks, healthcare providers are likely to consider more personalized monitoring and care for other specific cancers, as well as breast cancer.

Visit the FORCE website for guideline-recommended risk management published by gene mutation.

Knowing your risk after a first cancer diagnosis can help you work with your healthcare team to create a personalized plan that includes regular check-ups, prevention options and support from a genetic counselor who can guide you through your ongoing care and future risks.

Reference

Jones ME, Hounsome L, Kounali D, et al. Risk of Second Primary Cancer Among Patients With BRCA1 and BRCA2 Pathogenic Variants Diagnosed With Breast Cancer. Journal of Clinical Oncology 2024;42(22):2569-2580. 

Begg CB, Ostrovnaya I, Geyer FC, et al. Contralateral breast cancers: Independent cancers or metastases? International Journal of Cancer. 2018;142(2):347-356. 

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

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posted 12/11/25